Effect of L-tryptophan and L-leucine on biosynthesis of niacin-related compounds in Saccharomyces carlsbergensis

As a model system for investigating the mechanism of the hepatic NAD-lowering effect of leucine in rats, aerobically grown Saccharomyces carlsbergensis was used in this paper. Tryptophan supplementation of the medium doubled total niacin pro-duction by S. carlsbergensis. This elevation in total niacin was mainly due to increases in niacin (14 times) and niacinamide nucleotides (2 times). Among nucleotides, the NAD level doubled whereas NADH, NADP and NADPH levels dropped significantly. Simultaneous supplementation of the medium with leucine suppressed the elevation in total and free niacin levels. In the presence of tryptophan, approximately 50% of the total niacin was secreted in the medium in the form of free niacin, while in the presence of both tryptophan and leucine most of the total niacin remained in the cell. The specific activity of quinolinate phosphoribosyltransferase [EC 2.4.2.19] was not affected by supplementation of the medium with tryptophan and/or leucine. In contrast, the specific activity of nicoti-namide deamidase [EC 3.5.1.19] increased fivefold in the presence of tryptophan. Simultaneous supplementation of the medium with leucine suppressed the increase in nicotinamide deamidase. Cellular incorporation of tryptophan was not affected by leucine simul-taneously added as a supplement to the medium. Leucine did not have any inhibitory effect on total niacin synthesis from 3-hydroxyanthranilate. From the results, a possible mechanism for the inhibitory effect of leucine on the tryptophan-NAD pathway was discussed.